Ex vivo expansion of tumor-infiltrating lymphocytes from nasopharyngeal carcinoma patients for adoptive immunotherapy

Establishing Epstein-Barr virus (EBV)-specific cytolytic T lymphocytes (EBV-CTLs) from peripheral blood mononuclear cells (PBMCs) for adoptive immunotherapy has been reported in EBV-associated malignancies including Hodgkin's lymphoma and nasopharyngeal carcinoma (NPC). In the current study,we performed ex vivo expansion of tumor-infiltrating lymphocytes (TILs) obtained from NPC biopsy specimens with a rapid expansion protocol using anti-CD3 monoclonal antibody (OKT3), recombinant human interleukin (IL)-2, and irradiated PBMCs from healthy donors to initiate the growth of TILs. Young TIL cultures comprised of more than 90% of CD3+T cells, a variable percentage of CD3+CD8+and CD3+CD4+T cells, and less than 10% of CD3-CD16+natural killer cells, a similar phenotype of EBV-CTL cultures from PBMCs. Interestingly, TIL cultures secreted high levels of the Th1 cytokines, interferon gamma (IFNγ) and tumor necrosis factor-alpha (TNF-α), and low levels of the Th2 cytokines, IL-4 and IL-10. Moreover, young TILs could recognize autologous EBV-transformed B lymphoblast cell lines, but not autologous EBV-negative blast cells or allogeneic EBV-negative tumor cells. Taken together, these data suggest that ex vivo expansion of TILs from NPC biopsy tissue is an appealing alternative method to establish T cell-based immunotherapy for NPC.     

口腔鳞癌细胞增殖和细胞凋亡的相关性研究

目的：通过观察口腔鳞癌中细胞增殖和细胞凋亡之间的关系,探讨细胞凋亡在口腔鳞癌发生中的作用。方法：利用脱氧核糖核酸末端转移酶介导的dUTP缺口末端标记（TUNEL）技术及增殖细胞核抗原（PC—NA）免疫组织化学染色,对69例（维族36例、汉族33例）口腔鳞癌中的凋亡细胞和增殖细胞进行原位观察和比较。结果：口腔鳞癌不同组织学分级比较,高分化口腔鳞癌与中低分化口腔鳞癌之间增殖指数及凋亡指数均有显著性差异（P〈0．05）,不同部位的口腔鳞癌其增殖指数无显著差异,而舌癌组凋亡指数低于唇癌组和牙龈癌组（P〈0．05）,增殖指数与凋亡指数在口腔鳞癌中呈负相关关系（r=-0．663,P〈0．05）。结论：口腔鳞癌癌变过程不仅存在活跃的细胞增殖,而且存在细胞凋亡之异常,细胞增殖和细胞凋亡平衡失调在舌癌发病中可能起重要作用。     

肝细胞性肝癌根治性治疗后过继免疫治疗效果的Meta分析

目的:评价肝细胞性肝癌(HCC)术后过继免疫治疗(AIT)对预防复发及提高总生存率的疗效和安全性。方法:计算机检索Medline、Embase和Cochrane图书馆数据库中的相关文献。检索所有关于HCC术后AIT治疗的随机对照试验。结果:共纳入4个随机对照试验,合计423例患者。Meta分析结果显示,1)1年复发率:4个试验(n=423)表明,辅助AIT治疗组与单纯手术或射频消融治疗组比较,两组差异有统计学意义(RR=0.51,95%CI=0.36～0.71,P=0.000 1)。2)2个试验报道了3年复发率,两组差异无统计学意义(RR=0.76,95%CI=0.56～1.02,P=0.07)。3)死亡率:报道1年死亡率的2个研究显示,两组差异无统计学意义(RR=0.70,95%CI=0.31～1.61,P=0.41);3年死亡率结果亦显示差异无统计学意义(RR=0.76,95%CI=0.38～1.49,P=0.42)。4)不良反应:3篇研究报道了与辅助AIT治疗相关的不良反应,主要为寒战发热、头痛、头晕、恶心或心动过速。尚未见与AIT相关的感染、肝功能衰竭、自身免疫性疾病或死亡的报道。结论:辅助AIT治疗能降低HCC患者术后1年的复发率,但对改善生存率及远期复发率无明显作用。由于本研究纳入病例数较少,无法确定偏倚对结论可靠性的影响程度,因此,有必要开展多中心大样本及长期随访的随机对照试验来进一步证实。     

Clinical and biological considerations regarding glioma based on the TUNEL method and immunohistochemical staining using apoptosis-related antibodies

We examined 36 gliomas both by the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick-end-labeling (TUNEL) technique and by immunostaining of antibodies against apoptosis-related antigens. The apoptotic index (AI) obtained by the TUNEL method was 10.77±3.78% in astrocytomas, 6.19±1.81% in anaplastic astrocytomas, and 5.21±1.14% in glioblastomas. The AI of anti-Fas antibody and Le^Y antibody in gliomas also showed a similar tendency as the results with the TUNEL method. As a result, statistically significant differences were observed in the distribution of survival between the two groups according to the AI obtained by the TUNEL method. Therefore, an analysis of the AI is considered to be useful for prognosis.     

Systemic chemotherapy combined with local adoptive immunotherapy cures rats bearing 9L gliosarcoma

Summary Survival of Fischer rats bearing 9L gliosarcoma in the brain was measured to determine the efficacy of 1) systemically administered chemotherapy with local adoptive immunotherapy (chemo-adoptive immunotherapy) or 2) systemically administered chemo-immunotherapy. Winn assays, where tumor instillation coincided with the start of treatment, and one-week established tumor assays were conducted. Survival of chemo-adoptive immunotherapy treated groups given intraperitoneal cyclophosphamide and intracranial lymphokine activated killer cells and recombinant Interleukin-2 was significantly extended when compared to sham treated control groups, to groups given chemotherapy with intraperitoneal cyclophosphamide, and to groups treated by local adoptive immunotherapy with intracranial lymphokine activated killer cells and Interleukin-2. The killer cells were generated from spleens of donor rats that either had or had not been given cyclophosphamide 24 h earlier. Long-term survivors (9/39), sacrificed at day 70, were obtained only in the chemo-adoptive immunotherapy treated groups; 7/39 had no histologic evidence of tumor and had focal sterile abscesses at the site of killer cell instillation. Average group weight plotted over time showed that there was acceptable toxicity with chemo-adoptive immunotherapy; the toxicity was identical to that obtained with systemic cyclophosphamide treatment. In contrast, survival of chemo-immunotherapy treated groups given systemic cyclophosphamide and Interleukin-2 was not significantly extended from groups which were sham treated or treated only with systemic Interleukin-2. Rapid decline of average group weight plotted over time and early deaths following chemo-immunotherapy treatment indicated that the regimen was toxic. The effect of cyclophosphamide administration on the splenocytes of donor rats and the LAK cells generated from them was determined byin vitro studies analyzing cell number, viability, phenotypic expression and cytotoxicity against 9L tumor. In the treatment of this intracranial neoplasm, the beneficial effects of cyclophosphamide were determined to occurin situ in the tumor-bearing host. No benefit resulted from cyclophosphamide treatment of donor rats that supplied splenocytes for LAK cell production.     

33例头颈部恶性肿瘤患者局部过继免疫治疗的疗效观察

目的评价ＩＬ－２／ＬＡＫ细胞局部过继免疫疗法在头颈部恶性肿瘤治疗中的疗效。方法对３３例头颈部恶性肿瘤患者进行局部过继免疫治疗,采用ＩＬ－２每日１０～２０万单位局部注射,共１０天;于ＩＬ－２治疗的第４～８天同时于局部注射ＬＡＫ细胞１．０×１０８～５．０×１０８／ｄ。结果完全缓解１例,部分缓解６例,好转２０例,稳定６例,治疗总缓解率２１．２％,总有效率８１．８％。治疗后１,２,３年生存率分别为９６．３％、８３．３％、和７５．０％。组织病理学检查证实免疫治疗后肿瘤局部大量ＣＤ３、ＣＤ４阳性Ｔ淋巴细胞浸润。治疗过程中未见严重的毒副作用。结论局部应用ＬＡＫ细胞与ＩＬ－２治疗头颈部恶性肿瘤疗效明显,方法安全。     

免疫治疗联合放化疗治疗胶质母细胞瘤的研究进展

目前胶质母细胞瘤（glioblastoma,GBM）的标准治疗方法仍然是在最大安全程度的手术切除基础上辅以放化疗,但其5年生存率仍＜10%。免疫治疗如树突状细胞(dendritic cell,DC)疫苗、表皮生长因子受体突变体(EGFRvIII)疫苗、热休克蛋白（heat shock proteins,HSPs）疫苗等在临床试验中已经取得了巨大成就,临床III期试验也证明了免疫治疗与放化疗有协同作用。细胞毒性电离辐射是一种引起促炎信号级联免疫活化辅助细胞死亡的治疗方法,借此可以利用免疫治疗抗肿瘤。肿瘤免疫治疗的发展,使得免疫治疗可能成为继手术、放化疗后GBM治疗的另一个有效方法。寻找新的免疫治疗方法是未来GBM治疗的主要研究方向。本文就目前GBM的治疗策略及困境和放化疗联合免疫检查点抑制剂、DC疫苗以及EGFRvIII疫苗等免疫治疗研究进展作一综述。     

Combination of radiofrequency ablation and sequential cellular immunotherapy improves progression‐free survival for patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) recurs frequently after minimally invasive therapy. The aim of our study was to observe the efficiency and safety of the combined treatment of radiofrequency ablation (RFA) with cellular immunotherapy (CIT) for HCC patients. In our study, 62 patients with HCC who were treated with radical RFA were divided into two groups: RFA alone (32 patients) and RFA/CIT (30 patients). Autologous mononuclear cells were collected from the peripheral blood and separated by apheresis, and then induced into natural killer (NK) cells, γδT cells and cytokine‐induced killer (CIK) cells. These cells were identified by flow cytometry with their specific antibodies and then were infused intravenously to RFA/CIT patients for three or six courses. The tumor recurrent status of these patients was evaluated with computed tomography or magnetic resonance imaging every 3 months after RFA. Progression‐free survival (PFS), liver function, viral load and adverse effects were examined. The results implied that PFS was higher in RFA/CIT group than that in RFA group. In RFA/CIT group, six courses had better survival prognosis than three courses. Viral load of hepatitis C was decreased in two of three patients without antiviral therapy in RFA/CIT group, but was increased in RFA group. No significant adverse reaction was found in the patients with CIT. In summary, these preliminary results suggest that combination of sequential CIT with RFA for HCC patients was efficient and safe, and may be helpful in the prevention of the recurrence for the patients with HCC after RFA.     

Arsenic trioxide synergizes with B7H3-mediated immunotherapy to eradicate hepatocellular carcinomas

Arsenic trioxide (As(2)O(3)), a valuable anticancer drug for the treatment of acute promyelocytic leukemia, may also have therapeutic potential for the treatment of solid tumors. However, its therapeutic efficacy against solid tumors is lacking even at high dosages. Other therapeutic strategies are required to enhance the efficacy of As(2)O(3) against solid tumors such as hepatocellular carcinoma (HCC), which is refractory to chemotherapy. B7H3, a new member of the B7 family, has been shown to induce antitumor immunity. Intratumoral injection of B7H3 plasmids eradicates small EL-4 lymphomas, but monotherapy is ineffective against large tumors. Here we investigated whether As(2)O(3) would synergize with B7H3 immunotherapy to combat HCC. Large subcutaneous H22 HCCs (0.7-0.8 cm in diameter) established in BALB/c mice were rapidly and completely eradicated when intratumoral administration of As(2)O(3) was preceded by in situ gene transfer of B7H3. In contrast, neither As(2)O(3) nor B7H3 monotherapy was effective. The antitumor activity of As(2)O(3) was attributed to increased tumor-cell apoptosis, perhaps as a result of direct cytotoxicity as well as decreased tumor angiogenesis. Combination therapy generated potent systemic antitumor immunity mediated by CD8(+) and NK cells that was effective in combating a systemic challenge of 1 x 10(7) parental H22 cells. It led to the simultaneous and complete regression of multiple distant tumor nodules, concomitant with increased levels of serum IFN-gamma and cytotoxic T lymphocyte (CTL) activity. In conclusion, combining B7H3-mediated immunotherapy with As(2)O(3) warrants investigation as a therapeutic strategy to combat HCC, and other malignancies.     

Utility of FDG PET in patients with squamous cell carcinomas of the oral cavity

Background

The utility of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in oral cavity cancer has received little attention in a clinician's perspective. We systematically evaluated the clinical roles of FDG PET in patients with oral cavity squamous cell carcinomas (SCCs).

Methods

Between August 2001 and February 2005, 82 new patients with resectable oral cavity SCCs underwent CT/MRI and FDG PET at initial staging and follow-up. The sensitivity and specificity of CT/MRI and FDG PET for neck metastases were compared with histopathologic reference of 67 patients who underwent neck dissection. The relationships between the maximal standardized uptake value (SUV) of primary tumors and clinicopathologic parameters, such as gender, age, tumor thickness, local invasiveness, T and N categories, tumor-node-metastasis stage, and histological grade, as well as with disease-free survival (DFS), were assessed.

Results

FDG PET was more sensitive than CT/MRI for detecting cervical metastases on a level-by-level basis (38/43 vs. 28/43; P = 0.002). Age, T and N categories, tumor thickness (>8 mm) and SUV (>5.0) were also significant variables of 3-year DFS in univariate analysis. T category was an independent determinant of DFS in multivariate analysis (P < 0.05). During a mean follow-up of 36 months, FDG PET correctly diagnosed locoregional recurrences in 20 patients, distant metastases in six and second cancers in five.

Conclusion

FDG PET may have potential roles in initial staging, survival prediction, and the detection of recurrences and second cancers.     

口腔癌患者血清sIL－2R表达及其临床意义

采用双抗体夹心ＥＬＩＳＡ法对４０例口腔癌患者的血清可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）水平进行测定。结果发现口腔癌患者血清ｓＩＬ－２Ｒ水平显著高于正常对照组（Ｐ＜０．０１），并与临床分期有关；手术后血清ｓＩＬ－２水平较术前明显下降（Ｐ＜０．０１）；４例复发者血清ｓＩＬ－２Ｒ水平又见增高。因此，血清ｓＩＬ－２Ｒ水平的动态观察有助于口腔癌患者预后判断，并可监测复发与转移。     

活化自体淋巴细胞过继性免疫治疗在原发性肝细胞癌中的疗效观察

目的：评价活化自体淋巴细胞过继性免疫治疗（adoptive immunotherapy,AIT）是否有助于改善原发性肝细胞癌的临床疗效。方法：选取2016年8月至2018年12月在中国人民解放军总医院第五医学中心确诊的64例原发性肝细胞癌患者,通过分层随机法分为免疫治疗组（n=29）和对照组（n=35）。免疫治疗组患者取60 ml外周血分离制备单个核细胞并在含OKT-3和IL-2的培养基中活化培养,回输前进行质控检测。免疫治疗组中的Ⅰ~Ⅲ期患者（n=14）于一线治疗后接受自体淋巴细胞输注（3个月内输注6次）,Ⅳ期患者（n=15）仅接受自体淋巴细胞输注;对照组患者接受肝细胞癌相关的其他治疗。疗效评估的主要终点是2 年无复发生存（relapse-free survival,RFS）率,次要终点为无进展生存期（progression-free survival,PFS）和总生存期（overall survival,OS）。结果：入组患者中位随访时间为2.8年（0.2~4.2年）。免疫治疗组29名患者共接受了167次（计划174次,完成率96%）预定淋巴细胞输注（平均每人次回输9.30×109个细胞,其中CD3+HLA-DR细胞约占63%）,治疗期间未观察到3级或4级不良反应发生。与对照组相比,免疫治疗组患者2年RFS率显著升高（62.1% vs 22.9%,OR=0.181,95%CI：0.06~0.54,P=0.002）,中位PFS（28 vs 8个月,P=0.004）和中位OS（38 vs 34个月,P=0.915）均显著延长。在Ⅰ~Ⅲ期患者中,免疫治疗组（n=14）2年RFS率较对照组（n=18）显著升高（92.9% vs 33.3%,OR=0.38,95%CI：0.004~0.368,P=0.005）,中位PFS明显延长（38 vs 14.5个月,P=0.005）,而两组OS间无显著差异;Ⅳ期患者两组间PFS（P=0.077）及OS（P=0.994）均未见显著差异。结论：活化自体淋巴细胞AIT为安全可行的肝细胞癌辅助性治疗方法,可提高Ⅰ~Ⅲ期肝细胞癌一线治疗后RFS率、延长患者RFS时间,而对进展期肝细胞癌患者的PFS和OS无明显影响。     

异环磷酰胺联合自体PHA-LAK细胞治疗晚期复发卵巢上皮癌的疗效观察

目的研究异环磷酰胺(ifosfamide,IFO)联合自体PHA-LAK细胞过继性免疫治疗晚期复发卵巢上皮癌的疗效。方法25例复发的晚期卵巢上皮癌患者经IFO1200mg/(m2·d)连用4d,同时于用IFO后0、4、8h分别静脉推注美司钠400mg;化疗间歇期以PHA-LAK细胞治疗4次。联合治疗2个周期以上。结果25例患者中,完全缓解(CR)3例,部分缓解(PR)8例,稳定(NC)7例,进展(PD)7例,有效率(CR+PR)44%(11/25),中位无进展生存期(TTP)21周,中位生存期(OS)47周。毒副反应主要是消化道反应和骨髓抑制。结论IFO联合自体PHA-LAK细胞治疗复发的晚期卵巢上皮癌有效,毒副反应低,可作为晚期复发卵巢上皮癌的选择方案。     

恶性实体瘤患者自体细胞因子诱导杀伤细胞过继免疫治疗的安全性改进

目的观察恶性实体瘤患者外周血来源的细胞因子诱导杀伤细胞在自体血浆中的增殖特性及静脉回输治疗的安全性。方法用淋巴细胞分离液分离获取50例恶性实体瘤患者外周血单个核细胞,在含10%自体血浆的RPMI-1640培养液中添加rhIFN-γ、Anti-CD3mAb和rhIL-2联合诱导单个核细胞为细胞因子诱导杀伤细胞。在培养第13天进行细胞计数,通过流式细胞术检测细胞免疫表型,并将细胞进行自体回输。结果在培养第13天,细胞因子诱导杀伤细胞得到大量扩增,细胞数增加30.0±5.2倍。CD3 、CD3 CD4 、CD3 CD8 和CD3 CD16 CD56 细胞在培养第13天分别占(93.0±6.1)%、(28.4±7.2)%、(65.5±4.5)%和(25.8±12.2)%。恶性实体瘤患者回输自体细胞因子诱导杀伤细胞的治疗过程中未观察到明显的毒副作用,主要表现有畏寒、发热。结论恶性实体瘤患者血浆可以高效扩增自体细胞因子诱导杀伤细胞,临床应用安全可靠,且无明显的毒副作用。     

Randomized study of local control and survival following radical surgery or radiation therapy in oral and laryngeal carcinomas.

From 1971 to 1975, 100 patients with glottic, supraglottic, and oral cavity lesions were prospectively randomized between primary radiation treatment and primary surgery. Local control and survival were similar with either treatment for lesions of the oral cavity or supraglottic larynx. Comparison between radiation alone and surgery alone for T1 and T2 glottic laryngeal lesions showed local control rates of 76% and 100% (P=0.32); after secondary salvage attempts, local control rates were 82% and 100%, respectively (P= 0.52). Neither result approached statistical significance. Successful radiation for early glottic larynx lesions resulted in superior deglutition and equivalent voice function compared to successful primary treatment with conservation laryngectomy. For oral cavity lesions, swallowing was impaired in the same percentage of radiated and operated patients, but fewer primary radiation patients had articulation difficulties. Among the patients with supraglottic larynx lesions, aspiration was not a problem with either radiation or surgery, but successful radiation perhaps maintained a slightly better voice quality.     

Distinctive chromosomal instability patterns in oral verrucous and squamous cell carcinomas detected by high-resolution DNA flow cytometry

BACKGROUND:

Oral verrucous carcinomas (OVCs) are characterized by better prognosis than oral squamous cell carcinomas (OSCCs). Because chromosomal instability (CIN) in solid tumors is indicative of prognosis, this study investigated whether OVCs and OSCCs were characterized by differences in CIN biomarkers.

METHODS:

Fresh or frozen multiple tissue samples were submitted to high‐resolution DNA flow cytometry (hr DNA‐FCM).

RESULTS:

DNA aneuploid sublines were detected in 6 of 9 OVCs (66.7%) and in 20 of 25 OSCCs (80.0%). Multiple DNA aneuploid sublines were observed, respectively, in 2 of 6 (33.3%) DNA aneuploid OVCs and in 14 of 20 (70%) DNA aneuploid OSCCs (P = .163). OVCs were mainly characterized by DNA Index (DI) values in the near‐diploid region (DI≠1 and DI < 1.4), whereas aneuploid OSCCs carried most frequently multiple aneuploid sublines with high DI values (DI ≥ 1.4). DNA near‐diploid and high aneuploid sublines were, respectively, 87.5% and 12.5% for the OVCs versus 30% and 70% for the OSCCs (P = .004).

CONCLUSIONS:

Present data suggest that OVCs are characterized by a lower degree of CIN and tumor heterogeneity than OSCCs, such that they appear as “frozen” in an early stage of DNA near‐diploid aneuploidy, as previously observed for oral preneoplastic lesions. These DI characteristics, which can easily be obtained by hr DNA‐FCM, appear to reflect the well‐known differences in aggressiveness and prognosis of OVCs and OSCCs. Cancer 2011;. © 2011 American Cancer Society.     

Clinical efficacy of adoptive immunotherapy by IL-4 activated tumor-infiltrating lymphocytes in patients with advanced cancer

Background Adoptive immunotherapy using tumor-infiltrating lymphocytes (TILs) has been used to treat malignant melanoma and renal cell carcinoma, although the clinical efficacy of this method has not yet been proved. To improve clinical efficacy, it is important to induce sufficient amounts of tumor-infiltrating lymphocytes to fight the tumor. In this study, we investigated the clinical efficacy of adoptive immunotherapy using interleukin (IL)-2 activated tumor-infiltrating lymphocytes combined with IL-4. Methods Tumor-infiltrating lymphocytes from patients with non-malignant melanoma and non-renal cell carcinoma were cultured with IL-2 monotherapy (n=10) and combination therapy with IL-4+IL-2 (n=20). Comparing the 2 groups, we investigated the clinical benefits of adoptive immunotherapy, considering safety, clinical efficacy, survival periods, and quality of life. Results By using the IL-4+IL-2 combination, we successfully transferred 6.5 times more activated tumor-infiltrating lymphocytes, as compared to cell counts using IL-2 monotherapy. The response rate achieved was 58.8% (2 complete and 8 partial responses) without any side effects in the IL-4+IL-2 group. Furthermore, the IL-4+IL-2 group had longer survival periods and improved quality of life, compared to the IL-2 monotherapy group. Conclusion The IL-4+IL-2 combination improved the clinical efficacy of adoptive immunotherapy, and improved quality of life in patients with non-malignant melanoma and non-renal cell carcinoma.     

CIK细胞联合白介素-2对鼻咽癌病人免疫功能及EB病毒指标的影响

目的:细胞因子诱导杀伤细胞(cytokine-inducedkillercells,CIK细胞)是目前抗肿瘤过继细胞免疫治疗最为有效的方案。本研究通过治疗30例鼻咽癌病人,探讨CIK细胞联合IL-2对鼻咽癌病人免疫学功能及EB病毒指标的影响。方法:将符合条件的30例病人配对分为两组。治疗组病人接受CIK细胞过继细胞免疫治疗,每周一次,连续4周与对照组比较。免疫功能及EB病毒学指标分别通过测定外周血T淋巴细胞亚群,EB病毒VCA-IgA、EA-IgA、EDAb、DNA免疫荧光定量进行评估。结果:随访8～18个月,中位随访时间12个月。CIK治疗1个月后患者CD4 CD25 %明显下降,EB病毒VCA-IgA、EA-IgA、DNA免疫荧光定量下降显著。结论:CIK细胞可改善鼻咽癌病人的免疫功能,加速EB病毒抗体及DNA拷贝数下降。提示CIK治疗可消灭肿瘤微小残留灶及转移灶,可作为一种鼻咽癌的辅助治疗。     

CIK细胞联合白介素-2对鼻咽癌病人免疫功能及EB病毒指标的影响

目的：细胞因子诱导杀伤细胞（cytokine-induced killer cells，CIK细胞）是目前抗肿瘤过继细胞免疫治疗最为有效的方案。本研究通过治疗30例鼻咽癌病人，探讨CIK细胞联合IL-2对鼻咽癌病人免疫学功能及EB病毒指标的影响。方法：将符合条件的30例病人配对分为两组。治疗组病人接受CIK细胞过继细胞免疫治疗，每周一次，连续4周与对照组比较。免疫功能及EB病毒学指标分别通过测定外周血T淋巴细胞亚群，EB病毒VCA—IgA、EA—IgA、EDAb、DNA免疫荧光定量进行评估。结果：随访8—18个月，中位随访时间12个月。CIK治疗1个月后患者CD4^＋CD25^＋％明显下降，EB病毒VCA—IgA、EA—IgA、DNA免疫荧光定量下降显著。结论：CIK细胞可改善鼻咽癌病人的免疫功能，加速EB病毒抗体及DNA拷贝数下降。提示CIK治疗可消灭肿瘤微小残留灶及转移灶，可作为一种鼻咽癌的辅助治疗。     

恶性实体瘤患者自体PHA-LAK细胞过继性免疫治疗对淋巴细胞表型及功能的影响

目的：研究回输自体PHA-LAK细胞对恶性实体瘤患者淋巴细胞表型及功能状态的影响．方法：入组204例实体瘤患者．并以10例健康成人作为对照．采集与分离外周血单个核细胞，体外扩增PHA—LAK蜘胞，采用流式细胞术分析淋巴细胞表型．MTT法榆测淋巴细胞杀伤活性。结果：实体瘤患者较正常人淋巴细胞亚群CD3 ^ ／CD4^ 细咆、CD、3^ /CD8^ 细胞、B细胞、NK细胞减少，淋巴细胞杀伤活性下降。扩增的PHA-LAK是以激活的淋巴细咆亚群CD.^ ／CD8^ 细胞、CD3^ ／CD56^ 细胞、CD4^ ／CD2^ 细胞为主的异质性群体，其数量及杀伤活性明显增加，激话淋巴细胞标记性抗原分子表达亦增加：PHA-LAK细胞回输冶疗后．患者外周血上述激活淋巴细胞亚群数量增加．淋巴细胞系伤活性增强。结论：实体瘤患者淋巴细胞亚群数量及功能低下．PHA-LAK细胞过继性免痉治疗使患者体时激活淋巴细胞亚群数量增加．杀伤活性增强。